Validation Study of the Newly Proposed Refined Diagnostic Criteria for Malignant Phyllodes Tumor With 136 Borderline and Malignant Phyllodes Tumor Cases.

The World Health Organization (WHO) diagnostic criteria for malignant phyllodes tumor (MPT) may miss a significant number of MPTs with metastatic potential. New refined diagnostic criteria (Refined Criteria) for MPT were recently proposed. The aim of this study is to validate the Refined Criteria. This validation study included 136 borderline (borderline phyllodes tumor [BoPT]) and MPT cases that were not included in the initial study. We evaluated tumor classifications based on both the Refined Criteria and the WHO criteria. The Refined Criteria defines MPT when these criteria are met (1) stromal overgrowth with ≥ 1 feature(s) of marked stromal cellularity, marked stromal cytologic atypia, or ≥10 mitoses per 10 high-power fields (10 mitoses/10 HPFs) or (2) marked stromal cellularity with ≥1 feature(s) of marked stromal cytologic atypia, ≥10 mitoses/10 HPFs or permeative border. The WHO criteria require all 5 morphologic features (stromal overgrowth, permeative border, marked stromal cellularity, marked stromal cytologic atypia, and ≥10 mitoses/10 HPFs) for an MPT diagnosis. Using the Refined Criteria, none of the 61 BoPTs developed metastasis and 40.0% of the 75 MPTs developed metastases; local recurrence was seen in 11.5% BoPTs and 25.3% MPTs. Using the WHO criteria, 9.6% of the 94 BoPTs developed metastases and 50.0% of the 42 MPTs developed metastases; 14.9% of the BoPTs had local recurrence and 28.6% of the MPTs had local recurrence. Nine (30.0%) of the 30 tumors that developed distant metastases were diagnosed as BoPTs by the WHO criteria. When we combined the 75 MPTs from this validation cohort with the 65 MPT cases from the published data using the Refined Criteria, 50 (35.7%) of the 140 MPTs developed metastases, whereas 8 cases with metastases were <5 cm. In the univariate analysis with log-rank test, stromal overgrowth, marked stromal cellularity, marked stromal cytologic atypia, ≥10 mitoses/10 HPFs, presence of heterologous components other than liposarcomatous component, and presence of stromal necrosis were significantly associated with the risk of metastasis (all with P < 0.05). In multivariate analysis with Cox proportional hazard regression, stromal overgrowth and marked stromal cellularity were significantly associated with metastasis (both with P < 0.001). The Refined Criteria are superior to the WHO criteria in predicting the clinical outcomes of BoPTs and MPTs. Using the Refined Criteria, 35.7% of 140 patients with MPT developed metastases, whereas none (0%) of the patients with BoPT developed metastases. Patients with MPT have a high metastatic rate; these patients may benefit from systemic chemotherapy or targeted therapies. In contrast, patients with BoPT may be managed with complete local excision alone without chemotherapy.

Incidence of adult rib fracture injuries and changing hospitalization practice patterns: a 10-year analysis.

PURPOSE: Rib fractures are common after blunt thoracic trauma and can be associated with significant morbidity and mortality. We investigated trends of rib fracture injuries among adults presenting to United States (US) emergency departments, factors related to increased likelihood of hospitalization, and hospitalization practice patterns. METHODS: We queried the National Electronic Injury Surveillance System database between 2012 and 2021 for all patients 18 years of age and older with rib fractures. These data were extrapolated to provide national estimates. Regression analysis was performed to identify trends for injury and risk factors for hospitalization. RESULTS: We identified 32,233 adult patients with rib fractures; this extrapolated to a national estimate of 1,430,270 patients with rib fractures during the 10-year period. Between 2012 and 2021, there was a 52% increase in the incidence rate per 100,000 persons (R2 = 0.94, p < 0.001). Males accounted for 58% of patients with rib fractures, and 50% of patients were 65 years or older. Hospitalization was required in 38% of patients, and the hospitalization rate increased by 96% during the study period (R2 = 0.96, p < 0.001). When comparing hospitals of different sizes, a 20% greater increase in the odds of hospitalization over time was identified among patients presenting to "larger" hospitals compared to "smaller" hospitals. CONCLUSION: The incidence of rib fractures and the associated hospitalization rates are both increasing nationally, with half of cases occurring in patients aged 65 years or older. Our findings emphasize the urgent need to implement evidence-based preventive measures and current management guidelines when managing the increasing caseload of rib fracture injuries.

Correlation of HER2 Protein Level With mRNA Level Quantified by RNAscope in Breast Cancer.

Trastuzumab deruxtecan (T-DXd) has been approved by the US Food and Drug Administration (FDA) to treat patients with metastatic HER2-positive and HER2-low breast cancer, and clinical trials are examining its efficacy against early-stage breast cancer. Current HER2 immunohistochemical (IHC) assays are suboptimal in evaluating HER2-low breast cancers and identifying which patients would benefit from T-DXd. HER2 expression in 526 breast cancer tissue microarray (TMA) cores was measured using the FDA-approved PATHWAY and HercepTest IHC assays, and the corresponding RNA levels were evaluated by RNAscope. HER2 protein levels by regression analysis using a quantitative immunofluorescence score against cell line arrays with known HER2 protein levels determined by mass spectrometry were available in 48 of the cores. RNAscope was also performed in 32 metastatic biopsies from 23 patients who were subsequently treated with T-DXd, and the results were correlated with response rate. HER2 RNA levels by RNAscope strongly correlated with HER2 protein levels (P < .0001) and with HER2 IHC H-scores from the PATHWAY and HercepTest assays (P < .0001). However, neither protein levels nor RNA levels significantly differed between cases scored 0, ultralow, and 1+ by PATHWAY and HercepTest. The RNA levels were significantly higher (P = .030) in responders (6.4 ± 8.2 dots/cell, n = 12) than those in nonresponders (2.6 ± 2.2, n = 20) to T-DXd. RNAscope is a simple assay that can be objectively quantified and is a promising alternative to current IHC assays in evaluating HER2 expression in breast cancers, especially HER2-low cases, and may identify patients who would benefit from T-DXd.

Sofa and bed-related pediatric trauma injuries treated in United States emergency departments.

INTRODUCTION: Children under the age of 5 years suffer from the highest rates of fall-related injuries. Caretakers often leave young children on sofas and beds, however, falling and rolling off these fixtures can lead to serious injury. We investigated the epidemiologic characteristics and trends of bed and sofa-related injuries among children aged <5 years treated in US emergency departments (EDs). METHODS: We conducted a retrospective analysis of data from the National Electronic Injury Surveillance System from 2007 through 2021 using sample weights to estimate national numbers and rates of bed and sofa-related injuries. Descriptive statistics and regression analyses were employed. RESULTS: An estimated 3,414,007 children aged <5 years were treated for bed and sofa-related injuries in emergency departments (EDs) in the United States from 2007 through 2021, averaging 115.2 injuries per 10,000 persons annually. Closed head injuries (30%) and lacerations (24%) comprised the majority of injuries. The primary location of injury was the head (71%) and upper extremity (17%). Children <1 year of age accounted for most injuries, with a 67% increase in incidence within the age group between 2007 and 2021 (p < 0.001). Falling, jumping, and rolling off beds and sofas were the primary mechanisms of injury. The proportion of jumping injuries increased with age. Approximately 4% of all injuries required hospitalization. Children <1 year of age were 1.58 times more likely to be hospitalized after injury than all other age groups (p < 0.001). CONCLUSION: Beds and sofas can be associated with injury among young children, especially infants. The annual rate of bed and sofa-related injuries among infants <1 year old is increasing, which underscores the need for increased prevention efforts, including parental education and improved safety design, to decrease these injuries.

Supervised Learning in Multilayer Spiking Neural Networks With Spike Temporal Error Backpropagation.

The brain-inspired spiking neural networks (SNNs) hold the advantages of lower power consumption and powerful computing capability. However, the lack of effective learning algorithms has obstructed the theoretical advance and applications of SNNs. The majority of the existing learning algorithms for SNNs are based on the synaptic weight adjustment. However, neuroscience findings confirm that synaptic delays can also be modulated to play an important role in the learning process. Here, we propose a gradient descent-based learning algorithm for synaptic delays to enhance the sequential learning performance of single spiking neuron. Moreover, we extend the proposed method to multilayer SNNs with spike temporal-based error backpropagation. In the proposed multilayer learning algorithm, information is encoded in the relative timing of individual neuronal spikes, and learning is performed based on the exact derivatives of the postsynaptic spike times with respect to presynaptic spike times. Experimental results on both synthetic and realistic datasets show significant improvements in learning efficiency and accuracy over the existing spike temporal-based learning algorithms. We also evaluate the proposed learning method in an SNN-based multimodal computational model for audiovisual pattern recognition, and it achieves better performance compared with its counterparts.

Minicolumn-Based Episodic Memory Model With Spiking Neurons, Dendrites and Delays.

Episodic memory is fundamental to the brain's cognitive function, but how neuronal activity is temporally organized during its encoding and retrieval is still unknown. In this article, combining hippocampus structure with a spiking neural network (SNN), a new bionic spiking temporal memory (BSTM) model is proposed to explore the encoding, formation, and retrieval of episodic memory. For encoding episodic memory, the spike-timing-dependent-plasticity (STDP) learning algorithm and a proposed minicolumn selection algorithm are used to encode each input item into several active minicolumns. For the formation of episodic memory, a sequential memory algorithm is proposed to store the contexts between items. For retrieval of episodic memory, the local retrieval algorithm and the global retrieval algorithm are proposed to retrieve sequence information, achieving multisentence prediction and multitime step prediction. All functions of BSTM are based on bionic spiking neurons, which have biological characteristics including columnar and dendritic structures, firing and receiving spikes, and delaying transmission. To test the performance of the BSTM model, the Children's Book Test (CBT) data set was used to conduct a series of experiments under different settings, including changing the number of minicolumns, neurons and sequences, modifying sequence items, etc. Compared to other sequence memory algorithms, the experimental results show that the proposed BSTM achieves higher accuracy and better robustness.

GOLPH3 silencing inhibits adhesion of glioma U251 cells by regulating ITGB1 degradation under serum starvation.

GOLPH3, an oncoprotein, plays crucial roles in tumor etiology. Compelling evidences have demonstrated that GOLPH3 contributes to regulate tumor cell growth, migration and invasion under normal nutrient condition. However, the oncogenic activity of GOLPH3 under serum starvation remains largely unknown. In this study, we reported that GOLPH3 depletion led to marked reduction in adhesion of glioma U251 cells, particularly under serum deprivation. We found that silencing of GOLPH3 expression reduced the protein amount of ITGB1 only in serum-free medium. Further insights into the mechanism between GOLPH3 and ITGB1, we applied proteasome or lysosome inhibitor to block the degradation of ITGB1, and identified GOLPH3 silencing can prompt ITGB1 lysosomal degradation under serum starvation. Finally, we found the reductions in glioma cell adhesion and ITGB1 protein amount could be rescued by ITGB1 overexpression. Taken together, these results show that GOLPH3 contributes to the adhesion of glioma cells by regulating the lysosomal degradation of ITGB1 under serum starvation.

Development of a single base extension-tag microarray for the detection of pathogenic Vibrio species in seafood.

In this study, a single base extension-tag array on glass slides (SBE-TAGS) microarray was established to detect the seven leading seafood-borne pathogens, including Vibrio parahaemolyticus, Vibrio cholerae, Vibrio vulnificus, Vibrio mimicus, Vibrio alginolyticus, Vibrio anguillarum, and Vibrio harveyi. Three multiplex PCR assays were developed to specifically target the following species with individual gene markers, which are aadS, tdh, and trh for V. parahaemolyticus; col, toxR, and vvh for V. alginolyticus, V. mimicus, and V. vulnificus; and empA, vhh1, and tcpA for V. anguillarum, V. harveyi, and V. cholerae, respectively. The purified PCR products were used as template DNA for single base extension-tag reactions, labeled with Cy3 fluorescent dye and hybridized to DNA microarrays. The detection specificity of this microarray method was 100%, with the sensitivity for pure genomic DNA at 200 fg to 2 pg per reaction. Application of the DNA microarray methodology to 55 naturally contaminated seafood samples (shrimp, fish, and oysters) revealed the presence of V. parahaemolyticus at 50.9% and V. alginolyticus at 32.7%. This corresponds with traditional assays (microbiological and biochemical tests) except one sample which was identified as negative in V. parahaemolyticus by the microarray assay but as positive by the conventional method. Therefore, a combination of multiplex PCR with DNA microarray hybridization based on SBE-TAGS ensures rapid and accurate detection of pathogenic Vibrio species in seafood, thereby providing safer seafood products for consumers at a low financial burden to the aquaculture industry.